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The brain’s speech centre responds to universal and specific features of language
Publisher Correction: A red fluorescent genetically encoded biosensor for in vivo imaging of extracellular l-lactate dynamics
Associations of DNA methylation estimators of protein abundance with concurrent and future physical health risk factors
Abstract DNA methylation (DNAm) is an epigenetic modification which plays a role in gene regulation and has genetic and environmental influences. Recently, DNAm-based models of protein abundance (termed episcores) have been developed and were found to be associated with incident disease in older adults. Here, we ask if these episcores are associated with latent physical health phenotypes in children and young adults in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Episcores were projected in ALSPAC participants who had DNAm measurements in cord blood, and peripheral blood at ages seven, nine, 17, and 24 ( n = 192–2857). We analysed cross-sectional associations between 108 episcores and 17 physical health phenotypes, followed by an examination of prospective associations between episcores and the same phenotypes measured 2 + years after the blood samples used for episcore calculation. Two-sample Mendelian randomisation (2SMR) was then used to evaluate evidence for causal relationships between the underlying proteins and any associated physical health phenotypes. Of the associations tested between 17 physical health phenotypes and 108 episcores at multiple timepoints, 9 cross-sectional (CHIT1 is associated with 8 of these) and 11 prospective (SEMA3E is associated with 7 of these) phenotype-episcore associations were discovered. Of these, no 2SMR analyses suggested a causal effect of a protein on its related phenotype. We find evidence to suggest that episcores may be useful for discovering protein-phenotype associations in populations lacking direct measurements of protein abundance.
Tuning CAR-T cells by targeting cancer-associated glycan in pancreatic cancer
Abstract Chimeric antigen receptor (CAR) T cell therapy has transformed cancer treatment but its efficacy remains limited in solid tumors due to antigen heterogeneity, an immunosuppressive microenvironment, and the glycocalyx barrier. The glycocalyx, composed of dense glycoproteins such as MUC1, is markedly expanded in cancers, where it impedes immune cell access and antigen engagement, thereby reducing efficacy. In most adenocarcinomas, Tn antigen, comprising N-acetylgalactosamine linked to serine or threonine, is overexpressed. Tn-MUC1, a truncated form of MUC1 decorated with Tn antigen, is frequently overexpressed in pancreatic cancer. Here, we incorporate a non-signaling glyco-bridge binder recognizing Tn-MUC1 into mesothelin-directed CAR-T cells. This bridge enhances tumor recognition and cytotoxicity by increasing avidity and facilitating CAR activation in a density- and affinity-dependent manner. To broaden its applicability, we design a tandem Helix pomatia agglutinin (HPA) lectin-based bridge that recognizes Tn antigens across cancer types. CAR-T cells with the HPA-bridge exhibit superior cytotoxicity in pancreatic cancer models.
Defect-induced optical and thermoelectric properties of cobalt doped ZnO nanostructures prepared through hydrothermal route
De novo design of epitope-specific antibodies via a structure-driven computational workflow
An integrated approach to molecular profiling supports precision diagnosis of pediatric medulloblastoma in Argentina amid the resource-constrained setting
A recurrent pathogenic BRCA2 truncating variant reveals a role for BRCA2-PCAF complex in modulating NF-κB-driven transcription
Determination of optimum extraction conditions and evaluation of biological activities of Prunus Armeniaca L. (Apricot) fruit
From net-zero to zero-fossil in transforming the EU energy system
Abstract The EU climate neutrality goal requires a strong reduction in fossil fuel use. However, whether a complete phase-out is feasible and desirable remains unclear. Using an integrated assessment model, we quantify the additional effort needed to achieve a nearly complete EU-wide phase-out of fossil fuels by 2050 compared to a least-cost net-zero scenario. We show that in the least-cost scenario fossil fuel consumption already decreases by 90% from 2020 to 2050 and is compensated by renewable power, direct electrification, as well as some hydrogen and biofuels. However, hard-to-replace oil-based hydrocarbons and natural gas persist primarily in the chemical industry, aviation and shipping. Phasing them out requires the large-scale deployment of costly carbon-neutral e-fuels, which substantially increases marginal abatement costs from 460 EUR to 630 EUR tCO 2 -1 (500-1000 EUR tCO 2 -1 ). Our works shows the additional transformation challenges if the EU aims to strengthen its climate policy commitment with a full fossil phase-out target.
Deep learning–based artificial intelligence models predict survival in patients with oral cavity squamous cell carcinoma
Rising worldwide challenges to climate-induced extreme low-production events of photovoltaic and wind power
Exploring factors associated with occupational health risk among tannery workers in Bangladesh
Inhibition of adipocyte lipolysis by vaspin impairs thermoregulation in vivo
Abstract Altered activity of brown adipose tissue (BAT) contributes to obesity, insulin resistance, and cardiovascular disease. BAT secretes endocrine factors (“batokines”) that regulate thermogenesis. We identify the serpin vaspin as a batokine that modulates adrenergic control of lipolysis and thermogenesis. Adipocyte-specific vaspin overexpression in mice reduces BAT activation and impairs thermoregulation during cold exposure or fasting. Mechanistically, vaspin binds low-density lipoprotein receptors (LRP1, LDLR, vLDLR), inhibiting adrenergic signaling and lipolysis in brown and white adipocytes by modulating phosphodiesterase activity and endocytic lipid uptake. Gene set enrichment analyses in human subcutaneous adipose tissue and in vitro studies confirm vaspin’s anti-lipolytic effects in humans. Overall, vaspin emerges as a regulatory BATokine that fine-tunes BAT thermogenic activity to limit excessive energy expenditure and preserve metabolic balance.
A two-in-one lignosulfonate carbon dots for bacterial detection and fluorescence quenching in food, pharmaceuticals, and cultural heritage preservation
Abstract A versatile, multifunctional nanocomposite based on lignosulfonate (LS) and carbon dots (CDs) was developed and characterized to demonstrate its dual capability for selective antimicrobial activity and differential microbial sensing. Fourier-transform infrared (FTIR) spectroscopy confirmed the successful synthesis of the LS-CDs, showing new characteristic peaks corresponding to N–H, C–N, and C–S bonds. Structural analysis indicated that the synthesis process led to a more uniform and tightly packed pore distribution (2.03–3.53 μm) compared to the pure LS, which enhanced the composite’s surface properties. Quantum chemical parameters from Density Functional Theory (DFT) calculations supported these findings, revealing that the LS-CDs possess a higher polarity (µ = 9.29 Debye) and a lower energy gap (E g =0.0352 eV), signifying increased reactivity and a greater propensity for electron transfer. In biological assays, the LS-CDs exhibited no antimicrobial activity against the Gram-negative Escherichia coli , likely due to its protective outer membrane. However, the composite showed significant antimicrobial efficacy against the Gram-positive Staphylococcus aureus (16 mm inhibition zone) and the fungus Candida albicans (16 mm inhibition zone). This selective antimicrobial action is attributed to the strong electrostatic interactions between the LS-CDs and the simpler cell wall structures of these microorganisms, leading to cellular disruption. Furthermore, the LS-CDs demonstrated a remarkable differential sensing capability via unique fluorescence signals: a blue-to-red shift for E. coli , star-like green shapes for S. aureus , and red filaments for C. albicans . The observed fluorescence changes were accompanied by a sharp decrease in intensity from an initial value of 20.78 to final values of 6.46, 5.51, and 4.91, respectively, for E. coli , S. aureus , and C. albicans . This dual functionality positions the LS–CDs as a promising platform for applications in food safety, pharmaceutical quality control, and cultural heritage preservation.
The genetic architecture of brainstem structures
Modeling studies of the adsorption of Methyl Red and Acid Yellow 36 dyes by sulphonated Ulva lactuca carbon
Abstract This study investigated the adsorption of Acid Yellow 36 (AY36) and Methyl Red (MR) dyes using a novel sulfonated biochar carbon (GASC) synthesized from green algae ( Ulva lactuca ) via a reflux method in the presence of 80% sulfuric acid (H 2 SO 4 ). The structural and surface characteristics of the resultant GASC were evaluated by Fourier transform infrared spectroscopy (FTIR), Brunauer–Emmett–Teller (BET) surface area analysis, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). GASC exhibited a relatively low BET surface area of 6.27 m²/g, with a monolayer volume of 1.4392 cm³ (STP)/g. The total pore volume was measured as 0.0203 cm³/g, and the mean pore size was 12.971 nm. GASC’s total weight loss was 46.52%, indicating higher thermal stability compared to GAUL (78.01%). FTIR spectra validated the existence of many functional groups on GASC. Adsorption experiments for AY36 and MR dyes were conducted under varying conditions, including initial dye concentrations (50–150 mg/L), contact times (5–180 min), solution pH (2–12), and GASC dosages (0.5–1.5 g/L). According to the Langmuir isotherm, the maximum adsorption capacities ( Q m ) of GASC for AY36 and MR dyes were 216.45 and 454.55 mg g –1 , respectively. Kinetic assessments indicated that the adsorption of both dyes was optimally represented by the pseudo-second order model, validating the efficacy of the synthesized GASC as an adsorbent for eliminating AY36 and MR dyes from aqueous solutions. Furthermore, response surface methodology (RSM) and Artificial neural networks (ANN) were applied to model and optimize adsorption. Optimization of the adsorption parameters using the RSM study concluded that a maximum AY-36 dye removal percentage of 96.76% could be reached when employing 147.41 mg of GASC and 56.08 mg/L of AY-36 dye solution. The most significant degradation percentage of MR dye, 99.94%, was achieved using 132.34 mg of GASC and 59.30 mg/L of MR dye solution.